Digital x-ray breast tomosynthesis (XBT) is under development by major manufacturers of breast imaging equipment and is expected to become a clinical reality within the next few years. Although XBT is likely to improve the conspicuity of small masses compared to 2-D full field digital mammography (FFDM) by reducing the masking effect of superimposed fibroglandular breast tissue, it remains an anatomic imaging modality and therefore functional imaging modalities that can provide complementary information are desirable in order to improve specificity and positive predictive value. Molecular breast imaging (MBI) using compact gamma cameras permits functional imaging of the entire breast at high resolution and has shown promise as a complementary modality to FFDM. With the goal of obtaining functional image data that can be accurately correlated with the 3-D structural image data of XBT, our group has developed a unique dual modality tomographic (DMT) breast scanner that combines x-ray breast tomosynthesis and molecular breast imaging tomosynthesis (MBIT) on a single integrated gantry, thereby permitting accurate localization co- registration between 3-dimensional anatomic and functional image data. Our measurements have shown that compared to 2-D MBI, the use of MBIT greatly improves lesion contrast and image signal- to-noise ratio, especially for small, deep-seated lesions. The DMT scanner has been recently tested in a pilot clinical study and proved superior to XBT alone in specificity, positive predictive value, and accuracy. These preliminary results have motivated this application for funding to evaluate the scanner's clinical performance among a larger cohort of women. Prior to the proposed human study both the x-ray and molecular imaging components will be upgraded for greater detection efficiency (XBT and MBIT), shorter acquisition time (XBIT), lower noise (XBT), and improved patient positioning (XBT and MBIT). Potential clinical roles for DMT breast imaging include problem solving for women with equivocal mammographic/ultrasound studies, especially those with radiodense breasts; screening high-risk women, as an aid in biopsy target selection following a positive mammogram, particularly in patients with multiple suspicious areas; workup of palpable masses not demonstrated on mammography or ultrasound; cancer surveillance in patients with a personal history of breast cancer; pre-surgical planning for women with known cancer for determination of disease extent (multi-focal, contralateral breast); as an alternative to breast MRI for women for whom MRI is impossible because of NSF/NFD, obesity, claustrophobia, or who have cardiac pacemakers or other types of implants containing ferromagnetic components; and for monitoring response to neoadjuvant therapy.